Bリンパ球増殖・分化機構の解明とその異常制御に関する研究

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Interleukin 6 was originally identified as T cell-derived lymphokine which induced final differentiation of B cells and its cDNA was cloned. The study with recombinant IL-6 confirmed that IL-6 was one of the essential factor for B cells to produce antibody molecules. However, the studies demonstrated that IL-6 acted not only on B cells but showed a wide variety of biological functions on varions tissues and cells. For example it acts on T cells as cytotoxic T cell differentiation factor, on hematopoietic stem cells as multi-colony stimulating factor, on hepatocytes to induce acute phase proteins. It functions as myeloma/plasmacytoma growth factor and the result with myeloma cells from patients demonstrated that il-6 functioned as an autocrine growth factor for myeloma cells. Transgenic mice with human IL-6 gene generated plasmacytomas confirming that constitutive expression of IL-6 in B lineage cells in involved in oncogenesis of myeloma/plasmacytoma. The cDNA encoding for IL-6 receptor was also cloned and the deduced amino acid sequence showed that IL-6 receptor belongs to immunoglobulin superfamily. A second polypeptide chain involved for IL-6 signal transduction was also identified.The cDNA for lymphocyte Fcepsilon receptor (FcepsilonRII) was cloned. The sequence showed that FcepsilonRII had an unique structure, its C-terminus outside and N-terminal half of the molecule was shown to secrete as IgE binding factor and to be involved in the regulation of allergic reactions. FcepsilonRII was found to be identical with a B cell specific differentiation antigen, CD23. The presence of two different species of FcepsilonRII which were generated by differential RNA splicing mechanism and by the usage of different transcription initiation sites, was demonstrated. They were shown to be different in their intracytoplasmic portion and their expression was differently regulated.